IF: 0.957
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Different Clinical Presentations of Brucellosis


Mohammad Reza Hasanjani Roushan 1 , Soheil Ebrahimpour 1 , Zahra Moulana 1 , *


1 Infectious Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, IR Iran


Jundishapur Journal of Microbiology: 9 (4); e33765
Published Online: April 9, 2016
Article Type: Research Article
Received: October 26, 2015
Revised: January 16, 2016
Accepted: January 20, 2016




Background: Brucellosis is one of the important multi-organ zoonotic infectious diseases. The forms of the clinical course of brucellosis in humans are acute, sub-acute and chronic.

Objectives: The present study aimed to retrospectively analyze the clinical characteristics and complications in the clinical forms of human brucellosis in Iran.

Patients and Methods: The population included 957 patients admitted in the infectious diseases clinic affiliated to Babol University of Medical Sciences, Babol, Iran, within the past two decades. Data for the patients were obtained and documented in questionnaires. Patients were divided into three groups according to their history, symptoms and clinical presentation time: acute (0 - 2 months), sub-acute (3 - 12 months), and chronic (> 1 year).

Results: Most of the patients (73.8%) were in the acute stages of brucellosis, 22.6% had sub-acute brucellosis and 3.7% had chronic brucellosis. The most frequently observed symptoms were arthralgia (71%), sweating (66.7%), fever (57.2%) and backache (39.3%). The most common complication was arthritis (13.2%) in this study.

Conclusions: This infection was observed with a diversity of clinical manifestations. Therefore, diagnostic difficulty because of the various clinical presentations and the way to find undiagnosed complications should be investigated in the differential diagnosis of other diseases.


Brucellosis Signs and Symptoms Iran

Copyright © 2016, Ahvaz Jundishapur University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background

Brucellosis is one of the important multi-organ zoonotic diseases with annually more than 500,000 new cases worldwide (1). The epidemiological zone of this infection includes the Arabian Peninsula, Mediterranean basin, Indochina, some parts of central Asia and south America (2). In the endemic regions, many cases occur in females. Consumption of non-pasteurized dairy such as soft cheese, butter, ice cream is the most usual transmission manner of this infection (3). Yogurt and hard cheese have a lower risk than others due to lactic fermentation. The main complaints of the infected patients are fever, chills, night sweats, myalgia, anorexia, headache, joint pain and heart attacks (4, 5). The main symptom of brucellosis is fever with unknown origin; therefore, it can be misdiagnosed with similar pathologies such as all of fevers of unknown origin that may be caused by infectious diseases, malignancies, collagen vascular diseases including tuberculosis, malaria, rheumatic fever and leishmaniasis (6). The forms of the clinical course of brucellosis in humans are acute, sub-acute and chronic (7). To detect patients with the disease, medical history should be taken, and biochemical, hematological and serological test should be performed. In addition, microbiological tests such as Brucella spp. isolation, and molecular tests should also be done. Among serologic tests, standard agglutination test (SAT), 2-mercaptoethanol (2ME) test and Coombs test are routine. Infected patients are cured after more appropriate treatments, of course after months.

2. Objectives

The main important purpose of brucellosis treatment was to decline the involvement and signs of the disease. Irrespective of the suitable treatment, some patients have relapse of the disease symptoms since these bacteria are intracellular and can survive within macrophages. These confidants may cause chronic and relapse infection (8). The present study aimed to retrospectively analyze the clinical characteristics and complications in the clinical forms of human brucellosis.

3. Patients and Methods

The current study included patients diagnosed with brucellosis at the infectious diseases clinic affiliated to Babol University of Medical Sciences, Babol, Iran, within the past two decades. The files of the patients were retrospectively evaluated. All demographic characteristics such as age, gender, residency, risk factors and clinical manifestations of all admitted patients with brucellosis were exploited from their files and recorded in the questionnaires. The diagnosis of brucellosis was confirmed by representing standard agglutination test (SAT) ≥ 1.320 and 2-mercaptoethanol (2-ME) ≥ 1.80 for the patients with clinical signs and symptoms compatible with those of brucellosis. Patients were divided into three groups according to their history, symptoms and clinical presentation time: acute (0 - 2 months), sub-acute (3 - 12 months) and chronic (> 1 year) (9).

Diagnosis of musculoskeletal system complications was determined by the finding of swelling, effusion and limitation of motion in an involved joint and was confirmed by X-ray in the prone position. Moreover, spondylitis was diagnosed using magnetic resonance imaging (MRI). Genitourinary system involvement was diagnosed by finding swelling and tenderness of scrotal skin, testis and epididymis, with confirmation by sonography.

Endocarditis was diagnosed by elevation of anemia, cardiac murmur, and was confirmed by the detection of vegetations using echocardiography. Central nervous system (CNS) involvement was made by considering the presence of SAT positivity and abnormal findings obtained from cerebrospinal fluid (CSF) analyses (> 10 leukocyte/mm3, protein > 45 mg/dL, glucose < 2:3 of the blood glucose level). The SPSS ver. 17.0 was used for the statistical analysis of data.

4. Results

Overall, 957 patients with brucellosis were included in the study, 706 (73.8%) cases were acute, 216 (22.6%) sub-acute, and 35 (3.7%) were chronic. Among the patients 535 (55.9%) were male and 422 (44.1%) were female with the mean age of 34 ± 16.9 years (rang: 1 - 90). In terms of gender distribution, involvement with acute form of brucellosis regarding other clinical forms, occurs significantly in males 418 (59.2%) more than females 288 (40.8%) (P = 0.003).

Most of the patients, 421 (44.1%), were 21 - 40 years. While 238 (24.9%) case were < 20 years, 221 (23.1%) were 41 - 60 years and 77 (7.9%) patients were older than 60 years; therefore, age differences between the groups and all stages of disease were significant (P = 0.001).

More patients were from rural, 705 (73.8%), than the urban, 250 (26.2%), areas. Significant relationships were found between clinical forms of the disease and frequency of occupational exposure or risk factors in brucellosis (P = 0.01). The most common clinical manifestations were arthralgia, sweating, fever and backache in 679 (71%), 638 (66.7%), 547 (57.2%) and 376 (39.3%) cases, respectively. Between clinical features, only fever and backache had significant association with clinical forms.

The most frequent involvement was arthritis with 126 cases (13.2%), gastrointestinal complications 57 (6%), splenomegaly 49 (5.1%), sacroiliitis 46 (4.8%) and spondylitis with 44 (4.6%) cases. Complications were observed at all stages of infection but arthritis; spondylitis were significantly observed in patients with acute disease (P = 0.03, P = 0.001) respectively. Focal organs involvement such as epididymo-orchitis and respiratory system were presented in 40 (4.2%) and 22 (2.3%) of the cases respectively. Surprisingly, osteomyelitis, bursitis, cellulitis, CNS and skin involvements were not observed in chronic form of the disease.

Table 1. A Comparison of the Brucellosis Forms According to the Patient Characteristicsa
CharacteristicsTotal Patients (n = 957)Acute (n = 706 (73.8))Sub-Acute (n = 216 (22.6))Chronic (n = 35 (3.7))P Value
Male535 (55.9)418 (59.2)100 (46.3)17 (48.6)
Female422 (44.1)288 (40.8)116 (53.7)18 (51.4)
Urban250 (26.2)180 (25.6)59 (27.3)11 (31.4)
Rural705 (73.8)524 (74.4)157 (72.7)24 (68.6)
< 20238 (24.9)206 (29.2)28 (13.1)4 (11.4)
21 - 40421 (44.1)312 (44.2)95 (44.2)14 (40)
41 - 60221 (23.1)140 (19.9)65 (30.4)16 (45.7)
> 6077 (7.9)50 (7)26 (12.1)1 (2.9)
Mean age34 ± 16.932 ± 16.839 ± 16.439 ± 13.2
Risk factors439 (45.9)342 (48.4)78 (36.1)19 (54.3)0.01
Occupational exposure247 (25.8)195 (27.6)40 (11.5)12 (34.3)0.01
Fever547 (57.2)439 (62.2)99 (45.8)9 (25.7)0.000
Sweating638 (66.7)483 (68.4)134 (62)21 (60)0.1
Arthralgia679 (71)499 (70.7)153 (70.8)27 (77.1)0.7
Backache376 (39.3)254 (36)109 (50.5)13 (37.1)0.001
Anorexia32 (3.3)26 (3.7)5 (2.3)1 (2.9)0.6
Nausea and vomiting9 (0.9)8 (1.1)1 (0.5)00.5
Abdominal pain16 (1.7)12 (1.7)4 (1.9)00.7
cellulitis2 (0.2)2 (0.3)000.7
bursitis3 (0.3)2 (0.3)1 (0.5)00.8
Osteomyelitis1 (0.1)01 (0.5)00.2
Sacroiliitis46 (4.8)37 (5.2)9 (4.2)00.3
Spondylitis44 (4.6)20 (2.8)22 (10.2)2 (5.7)0.000
Arthritis126 (13.2)104 (14.7)21 (9.7)1 (2.9)0.03
polyarthritis19 (2)12 (1.7)5 (2.3)2 (5.7)0.2
Epididymo-orchitis40 (4.2)33 (4.7)7 (3.2)00.2
Splenomegaly49 (5.1)39 (5.5)10 (4.6)00.3
Skin involvement5 (0.5)5 (0.7)000.4
Respiratory system involvement22 (2.3)19 (2.7)3 (1.4)00.3
CNS involvement2 (0.2)1 (0.1)1 (0.5)00.6
GI complications57 (6)46 (6.5)10 (4.6)1 (2.9)0.4

aValues are expressed as No. (%) or mean ± SD.

5. Discussion

Brucellosis is a public health problem that can cause severe significant disability and complications (10). According to the annual report of world health organization (WHO), Iran is an endemic region (11). Brucellosis can occur in both genders and any age group (12). In the current study, 535 (55.9%) of the patients were male and 422 (44.1%) were female with a mean age of 34 ± 16.9 years which was similar to some other studies (13). In some studies, the female ratio was reported more than that of the male (14). Overall, the prevalence of brucellosis can occur at any age but is common in adults and young people (15). In the current study the most common age group was 21 - 40 years, 421 patients (44.1%), which was similar to other studies (16). Of this age group 312 (44.2%) were acute, 95 (44.2%) sub-acute and 14 (40%) were chronic. These results show how age range reflects socio- economic and cultural status of this infection in an endemic area. Some studies reported older mean age groups usually working on farms with dairy production; therefore, brucellosis is more frequently occurs in this age group (17).

The current study results were similar to some studies presenting that brucellosis was still endemic in rural areas, but rare in urban areas (18). In the north of Iran, the rate of population involved in this infection in rural areas is more than that of the urban areas. In recent years human brucellosis cases have spread from rural to urban regions (19). A recent study found an overall 247 (25.8%) of patients in high risk occupational groups. Many previous studies overlooked some of these important at risk occupational groups (20).

The primary transmission route of brucellosis is by the ingestion of unpasteurized dairy products in the endemic countries; whereas in the developed countries infection occurs mostly due to occupational exposure (21). Similar to other studies, the majority of patients, 439 (45.9%) cases, had risk factors such as history of consuming unpasteurized milk or milk products (22). In contrast to the current study results about residency and risk factors, some experts showed that chronic brucellosis were from rural areas because of consumption of unpasteurized dairy products or contact with animals (9).

Brucellosis seems to affect human immune system and can cause acute, sub-acute and chronic clinical features. In the present study, 73.8%, 22.6% and 3.7% of the patients had the acute, sub-acute and chronic forms of the disease, respectively. But the study by Eini et al. presented that 24% of the patients had acute brucellosis, 70.8% were in sub-acute stages and 5.2% had chronic brucellosis (23). Acute form in different genders was compared (male: 59.2% vs. female: 40.8%). In another study by Keramat et al. 178 patients (58.9 %) with acute brucellosis were male (13).

Most patients had brucellosis with the main clinical symptoms of being arthralgia, sweating, fever and backache; findings were similar to the results obtained by the others working in endemic regions (24). Moreover, typically cases with acute brucellosis present signs such as fever, fatigue, chills and sweating (25). In this study, 71% of the patients had arthralgia and in terms of clinical type, 70.7% had the acute form. The results of the current study were similar to those of the studies in other countries; and arthritis was the most common complications of brucellosis (22). On physical examination, sweating (66.7%) and fever (57.2%) were mostly observed in the acute form the disease. Another study identified a significant correlation between fever and the acute form of brucellosis (26). Similar to the study by Aygen et al. in which the most frequent symptoms were fever (63.2%), sweating (62.7%), arthralgia (59.1%) and back pain (58.5%) (27).

Brucellosis complications are a major medical problem in countries where the infection is still endemic. The prevalence of focal involvement has been reported to range from 20% to 40% in many studies (28). Arthritis occurred for the first time in the patients with the acute form. It was one of the main presented clinical features. In the current study, arthritis involvement was observed in 14.7%, 9.7% and 2.9% of the patients with acute, sub-acute and chronic brucellosis, respectively. Geyik et al. showed that sacroiliitis and polyarthritis were more frequent complications in acute cases (29). In a recent study, spondylitis occurred in 2.8%, 10.2% and 5.7% of the patients with acute, sub-acute and chronic disease, respectively.

According to Bodur et al. spondylitis was observed in 12 (46%) and 13 (50%) patients with acute and sub-acute brucellosis (30). Brucellosis is a common disease which may occur in different forms. In Iran, people should be taught to avoid consumption unpasteurized dairy products and contact with infected animals. This infection was observed with a diversity of clinical manifestations. Therefore, due to the various clinical presentations and undiagnosed complications, diagnosis of brucellosis is difficult. Hence, differential diagnosis of the infection should be investigated in the further studies.

1 Kassiri H, Amani H, Lotfi M. Epidemiological, laboratory, diagnostic and public health aspects of human brucellosis in western Iran. Asian Pac J Trop Biomed. 2013; 3(8): 589-94[DOI][ PubMed ]
2 Hendaus MA, Qaqish RM, Alhammadi AH. Neurobrucellosis in children. Asian Pac J Trop Biomed. 2015; 5(2): 158-61[DOI]
3 Roushan MR, Amiri MJ. Update on childhood brucellosis. Recent Pat Antiinfect Drug Discov. 2013; 8(1): 42-6[ PubMed ]
4 Mantur BG, Biradar MS, Bidri RC, Mulimani MS, Kariholu P, et al. Protean clinical manifestations and diagnostic challenges of human brucellosis in adults: 16 years' experience in an endemic area. J Med Microbiol. 2006; 55: 897-903[DOI][ PubMed ]
5 Bingol A, Togay-Isikay C. Neurobrucellosis as an exceptional cause of transient ischemic attacks. Eur J Neurol. 2006; 13(5): 544-8[DOI][ PubMed ]
6 Cunha BA, Hage JE, Nouri Y. Recurrent fever of unknown origin (FUO): aseptic meningitis, hepatosplenomegaly, pericarditis and a double quotidian fever due to juvenile rheumatoid arthritis (JRA). Heart Lung. 2012; 41(2): 177-80[DOI][ PubMed ]
7 Galinska EM, Zagorski J. Brucellosis in humans--etiology, diagnostics, clinical forms. Ann Agric Environ Med. 2013; 20(2): 233-8[ PubMed ]
8 Castano MJ, Solera J. Chronic brucellosis and persistence of Brucella melitensis DNA. J Clin Microbiol. 2009; 47(7): 2084-9[DOI][ PubMed ]
9 Hasanjani Roushan MR, Mohrez M, Smailnejad Gangi SM, Soleimani Amiri MJ, Hajiahmadi M. Epidemiological features and clinical manifestations in 469 adult patients with brucellosis in Babol, Northern Iran. Epidemiol Infect. 2004; 132(6): 1109-14[ PubMed ]
10 Rahil AI, Othman M, Ibrahim W, Mohamed MY. Brucellosis in Qatar: A retrospective cohort study. Qatar Med J. 2014; 2014(1): 25-30[DOI][ PubMed ]
11 Zeinali M, et al. National guidelines against brucellosis [in Persian] 2012;
12 Jama'ayah MZ, Heu JY, Norazah A. Seroprevalance of brucellosis among suspected cases in Malaysia. Malays J Pathol. 2011; 33(1): 31-4[ PubMed ]
13 Ranjbar M, Keramat F, Mamani M, Kia AR, Khalilian FO, Hashemi SH, et al. Comparison between doxycycline-rifampin-amikacin and doxycycline-rifampin regimens in the treatment of brucellosis. Int J Infect Dis. 2007; 11(2): 152-6[DOI][ PubMed ]
14 Sari I, Altuntas F, Hacioglu S, Kocyigit I, Sevinc A, Sacar S, et al. A multicenter retrospective study defining the clinical and hematological manifestations of brucellosis and pancytopenia in a large series: Hematological malignancies, the unusual cause of pancytopenia in patients with brucellosis. Am J Hematol. 2008; 83(4): 334-9[DOI][ PubMed ]
15 Zeinalian Dastjerdi M, Fadaei Nobari R, Ramazanpour J. Epidemiological features of human brucellosis in central Iran, 2006-2011. Public Health. 2012; 126(12): 1058-62[DOI][ PubMed ]
16 Fallatah SM, Oduloju AJ, Al-Dusari SN, Fakunle YM. Human brucellosis in Northern Saudi Arabia. Saudi Med J. 2005; 26(10): 1562-6[ PubMed ]
17 Savas L, Onlen Y, Savas N, Yapar AF, Aydin M, Tugal O. Prospective evaluation of 140 patients with brucellosis in the southern region of Turkey. Infect Dis Clin Pract. 2007; 15(2): 83-8
18 Wong TM, Lou N, Jin W, Leung F, To M, Leung F. Septic arthritis caused by Brucella melitensis in urban Shenzhen, China: a case report. J Med Case Rep. 2014; 8: 367[DOI][ PubMed ]
19 Chen S, Zhang H, Liu X, Wang W, Hou S, Li T, et al. Increasing threat of brucellosis to low-risk persons in urban settings, China. Emerg Infect Dis. 2014; 20(1): 126-30[DOI][ PubMed ]
20 Beheshti S, Rezaian GR, Azad F, Faghiri Z, Taheri F. Seroprevalence of brucellosis and risk factors related to high risk occupational groups in Kazeroon, South of Iran. Int J Occup Environ Med. 2010; 1(2): 62-8[ PubMed ]
21 Alavi SM, Motlagh ME. A review of epidemiology, diagnosis and management of brucellosis for general physicians working in the Iranian health network. Jundishapur J Microbiol. 2012; 5(2): 384-7[DOI]
22 Ayazi P, Mahyar A, Rasoli A. Brucellosis in Children. J Comprehens Pediatr. 2012; 3(1): 12-5
23 Eini P, Keramat F, Hasanzadehhoseinabadi M. Epidemiologic, clinical and laboratory findings of patients with brucellosis in Hamadan, west of Iran. J Res Health Sci. 2012; 12(2): 105-8[ PubMed ]
24 Diju IU. Brucellosis--an under-estimated cause of arthralgia &amp; muscular pains in general population. J Ayub Med Coll Abbottabad. 2009; 21(2): 128-31[ PubMed ]
25 Buzgan T, Karahocagil MK, Irmak H, Baran AI, Karsen H, Evirgen O, et al. Clinical manifestations and complications in 1028 cases of brucellosis: a retrospective evaluation and review of the literature. Int J Infect Dis. 2010; 14(6)-78[DOI][ PubMed ]
26 Kurtaran B, Candevir A, Inal AS, Komur S, Akyildiz O, Saltoglu N, et al. Clinical appearance of brucellosis in adults: fourteen years of experience. Turk J Med Sci. 2012; 42(3): 497-505
27 Aygen B, Doganay M, Sumerkan B, Yildiz O, Kayabas U. Clinical manifestations, complications and treatment of brucellosis: a retrospective evaluation of 480 patients. Medecine et Maladies Infect. 2002; 32(9): 485-93
28 Colmenero JD, Reguera JM, Martos F, Sanchez-De-Mora D, Delgado M, Causse M, et al. Complications associated with Brucella melitensis infection: a study of 530 cases. Medicine (Baltimore). 1996; 75(4): 195-211[ PubMed ]
29 Geyik MF, Gur A, Nas K, Cevik R, Sarac J, Dikici B, et al. Musculoskeletal involvement of brucellosis in different age groups: a study of 195 cases. Swiss Med Wkly. 2002; 132(7-8): 98-105[ PubMed ]
30 Bodur H, Erbay A, Colpan A, Akinci E. Brucellar spondylitis. Rheumatol Int. 2004; 24(4): 221-6[DOI][ PubMed ]